PB1181 - Plasma proteomic profiles of patients during anticoagulant treatment with vitamin K antagonists.

Tuesday, June 25, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

Eleonora Camilleri, MD

MD PhD candidate
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands
Leiden, Zuid-Holland, Netherlands

Co-Author(s)

Bv

Bart JM van Vlijmen

PhD, associate professor
Department of Thrombosis & Hemostasis, Leiden University Medical Center, Leiden, The Netherlands
Leiden, Zuid-Holland, Netherlands
MW

Manfred Wuhrer

PhD, prof
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherland
Leiden, Zuid-Holland, Netherlands
CB

Christoph H. Borchers

Prof
Gerald Bronfman Department of Oncology, McGill University, Montreal, Canada
Montreal, Quebec, Canada
Suzanne C. Cannegieter

MD, PhD, prof
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Leiden, Zuid-Holland, Netherlands
Nienke van Rein

PhD
Leiden University Medical Center, department of Clinical Pharmacy and Toxicology and Clinical Epidemiology
Leiden, Zuid-Holland, Netherlands
Yassene Mohammed

PhD, assistant professor
Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherland
Leiden, Zuid-Holland, Netherlands

Background: Quantitative targeted proteomics is a promising technique for characterizing biological samples. Its advantages are precise and reproducible determination of biomarkers. As currently underutilized in thrombosis, differences in proteomic profiles per relevant subgroups are unknown.

Aims: To profile the plasma proteome of patients during anticoagulant treatment with vitamin K antagonists (VKAs), investigating differences by age, sex and treatment indication.

Methods: We measured 270 proteins in a random subcohort of patients included in the BLEEDS cohort, which enrolled 16,570 patients initiating VKAs between 2012-2014 (with plasma available in 83%). We used quantitative targeted proteomics with internal standards to quantify proteins, using a previously developed assay. The panel includes among others coagulation and fibrinolytic proteins, complement, immunoglobulins and apolipoproteins. Concentrations were compared between older (≥70y) and younger ( < 70y) patients, sex (male vs female) and treatment indication (atrial fibrillation[AF] and venous thromboembolism[VTE]) with Wilcoxon rank-sum test (p-value≤0.05 adjusted for false discovery rate). Proteins were assessed for collinearity and subgroups for interaction using regression models.

Results: 139/270 proteins passed the quantification criteria in a random subset of 362 patients initiating VKAs. Patients had a median age of 70 years and 139(53%) were male. The main treatment indication was AF(257, 71%) followed by VTE(71, 20%). Proteomic profiles were specific according to age, with older patients having higher levels of alpha-2-macroglobulin, fibulin and complement factors, among others (Figure 1). Pregnancy zone protein was lower in males compared to females, and showed interaction with age. Patients with VTE had elevated levels of apolipoprotein C-I, B-100, L-1 and A-II compared with AF patients (Figure 2). Proteoglycan-4 levels were also increased in VTE patients compared to AF. Patients with pulmonary embolism had a similar profile compared to deep vein thrombosis patients.

Conclusion(s): Patients during anticoagulant treatment have age and sex-specific proteomic profiles. Elevated levels of apolipoproteins are a specific signature of VTE patients.